Electroacupuncture promotes microglial M2 polarization in ischemic stroke via annexin A1.

Abstract

BACKGROUND:

Neuroinflammation is the leading cause of neurological sequelae in ischemic stroke. Recently, we reported that the anti-inflammatory mediator annexin A1 (ANXA1) favored microglial M2 polarization in brain injury. The purpose of this study was to investigate electroacupuncture (EA) treatment and its potentially ANXA1-mediated anti-inflammatory effects in the middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model of stroke.

METHODS:

Treatment with EA consisted of dense-sparse frequencies (alternating 4 Hz sparse waves for 1.5 s and 16 Hz dense waves for 1.5 s) at CV24 and GV26. Intracerebroventricular (ICV) injection of Boc-2 (5 µM) or short hairpin RNA (sh)ANXA1 (2 µL) 3 days before EA was performed to block the effects of ANXA1.

RESULTS:

EA pretreatment enhanced expression of ANXA1 and its receptor, formyl peptide receptor (FPR), when compared to MCAO/R alone. EA treatment also rescued MCAO/R-induced deficits in neurological performance, and learning and memory, and reduced infarct volume. Double immunofluorescent labeling showed that EA prevented MCAO/R-induced changes in microglial activation and morphology. EA also reduced the release of pro-inflammatory cytokines, such as interleukin (IL)-1β, inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α, while increasing the release of anti-inflammatory cytokines, such as arginase-1 (Arg-1) and brain-derived neurotrophic factor (BDNF). All EA-induced effects were either partially or completely prevented by prior administration of FPR antagonist Boc-2 or shANXA1.

CONCLUSION:

The current study provides strong evidence that EA treatment has protective effects against ischemic stroke in the MCAO/R mouse model and that the mechanism likely involves the promotion of M2 polarization in microglia via ANXA1.

• Authors: Jing Zou, Guo-Fu Huang, Qian Xia, Xing Li, Jing Shi, Ning Sun
• Journal: Acupuncture in medicine : journal of the British Medical Acupuncture Society (Acupunct Med) Vol. 40 Issue 3 Pg. 258-267 (06 2022) ISSN: 1759-9873 [Electronic] England
• PMID: 34894768 (Publication Type: Journal Article)

Chemical References

• Annexin A1
• Cytokines
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Annexin A1 (genetics, metabolism)
• Brain Ischemia (genetics, metabolism, therapy)
• Cytokines (metabolism)
• Disease Models, Animal
• Electroacupuncture
• Infarction, Middle Cerebral Artery (metabolism, therapy)
• Ischemic Stroke (therapy)
• Mice
• Microglia
• Stroke (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)